Diabetes mellitus is a widespread disease, and the diagnosis is based upon elevated blood glucose levels.
There are at least two subtypes of the disease: type 1 or insulin dependent diabetes mellitus, and type 2 non insulin dependent diabetes mellitus. Worldwide the number of diabetics is steadily increasing, especially in the group with type 2 diabetes, where up to 10% of the older generation (&gt;65 years of age) in the western hemisphere will suffer from type 2 diabetes.
The separation of the two subclasses is based on pathophysiological and clinical findings. In type 1 diabetes the insulin producing .beta.-cells in pancreas are destroyed by a selective auto immune reaction. The clinical outcome is due to the absolute insulin deficiency, and these patients will die from the disease unless treated with insulin regularly.
The underlying pathophysiological mechanisms in type 2 diabetes are not fully clarified. The various tissues are less sensitive to insulin (insulin resistance). The .beta.-cell function is partially preserved, and the type 2 diabetic patients secrete enough insulin to be protected from the development of diabetic coma--eventually leading to exitus.
However, the insulin secretion pattern is altered in connection with meals, as the increase is too slow and protracted and unable to normalize the blood glucose profile. In more severe cases the .beta.-cell function is also decreased in the fasting state, and fasting blood glucose becomes elevated as well. The normal, complex regulation of the .beta.-cell function is disturbed in type 2 patients. This regulation include the effect of different substrates (e.g. glucose, alanine), and hormones (e.g. glucagon), which may increase or decrease the insulin release. Furthermore the secretion is also regulated via .alpha.- and .beta.-adrenergic nerve fibres. It is striking that especially glucose becomes less effective as an insulin-releasing agent in type 2 diabetics as the disease becomes more severe.
According to current recommendations all type 2 patients are prescribed a diabetes diet, and some patients achieve acceptable blood glucose levels on diet alone. However, the majority of patients needs some kind of medical treatment as well. The standard approach is to prescribe a sulphonylurea, which will cause an increase in insulin secretion. Sulphonylureas are effective even at normal or low levels of blood glucose. Therefore there is a considerable risk of the occurence of severe hypoglycaemia on sulphonylurea treatment, and even fatal cases have been reported.
Good glycaemic control (i.e. constant blood glucose values near normal levels) is officially recommended as the only way to protect patients from the diabetic micro- and macro-vascular complications, such as blindness, renal failure, acute myocardial infarction, gangrene, etc. However, many patients are reluctant to follow this strategy, as they anticipate a higher number of severe hypoglycaemic attacks.